The main objective of this project has been and will continue to be to perform prospective, longitudinal studies on the natural history of CMV infection in pregnant women, and their offspring to identify pathogenetic factors for intrauterine infection. Our current working hypotheses are that primary maternal infections are more likely to be associated with transmission of virus in utero and virulent fetal infections than are recurrent maternal infections, and that early gestational infections are more dangerous for the fetus than are later ones (Specific Aims 1 and 2). We now propose that CMV infection acquired in utero and in early infancy may predispose females to increased bouts of reactivated latent infections during childbearing years and account, in part, for increased frequency of congenital infection with recurrent maternal infection in low income populations (Specific Aim 3). We further propose that genetically controlled maternal factors, such as the amount of virus generated, with either primary or recurrent infections influence whether the placenta becomes infected and thereby whether the virus is transmitted in utero or not (Specific Aim 5). We also plan to investigate the role of the placenta as a barrier to intrauterine transmission of virus with primary maternal infection and as a possible modulator, along with maternal immunity, of the virulence of the fetal infection (Specific Aim 4).